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Biochimie. 2019 Jan 14. pii: S0300-9084(19)30007-0. doi: 10.1016/j.biochi.2019.01.007. [Epub ahead of print]

M17 aminopeptidases diversify function by moderating their macromolecular assemblies and active site environment.

Author information

1
Biomedicine Discovery Institute, Department of Microbiology, Monash University, Melbourne, VIC, 3800, Australia.
2
Biomedicine Discovery Institute, Department of Microbiology, Monash University, Melbourne, VIC, 3800, Australia. Electronic address: sheena.mcgowan@monash.edu.

Abstract

The family of M17 aminopeptidases (alias 'leucine aminopeptidases', M17-LAPs) utilize a highly conserved hexameric structure and a binuclear metal center to selectively remove N-terminal amino acids from short peptides. However, M17-LAPs are responsible for a wide variety of functions that are seemingly unrelated to proteolysis. Herein, we aimed to investigate the myriad of functions attributed to M17. Further, we attempted to differentiate between the different molecular mechanisms that allow the conserved hexameric structure of an M17-LAP to mediate such diverse functions. We have provided an overview of research that identifies precise physiological roles of M17-LAPs, and the distinct mechanisms by which the enzymes moderate those roles. The review shows that the conserved hexameric structure of the M17-LAPs has an extraordinary capability to moderate different molecular mechanisms. We have broadly categorized these mechanisms as 'aminopeptidase-based', which include the characteristic proteolysis reactions, and 'association-driven', which involves moderation of the molecule's macromolecular assembly and higher order complexation events. The different molecular mechanisms are capable of eliciting very different cellular outcomes, and must be regarded as distinct when the physiological roles of this large and important family are considered.

KEYWORDS:

Cysteinylglycinase; Cytosol aminopeptidase; Leucine aminopeptidase; Leucyl aminopeptidase; M17; Metalloenzyme

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